Search Results (140)

Poorly differentiated thyroid malignancy, a rare histological type of aggressive thyroid malignancy with associated difficulties and gaps in its histological and molecular characterization, might lead to challenging clinical presentations that require a prompt multimodal approach. This case study involved a 56-year-old, non-smoking male with a rapidly developing goiter (within 2–3 months) in association with mild, non-specific neck compressive symptoms. His medical history was irrelevant. A voluminous goiter with substernal and posterior extension up to the vertebral bodies was detected using an ultrasound and computed tomography (CT) scan and required emergency thyroidectomy. He had normal thyroid function, as well as negative thyroid autoimmunity and serum calcitonin. The surgery was successful upon “Y” incision, which was used to give better access to the retrosternal component in order to avoid a sternotomy. Post-operatively, the subject developed hypoparathyroidism-related hypocalcemia and showed a very high serum thyroglobulin level (>550 ng/mL). The pathological report confirmed poorly differentiated, multifocal thyroid carcinoma (with an insular, solid, and trabecular pattern) against a background of papillary carcinoma (pT3b, pN0, and pM1; L1; V2; Pn0; R1; and stage IVB). The subject received 200 mCi of radioiodine therapy for 6 weeks following the thoracic surgery. Whole-body scintigraphy was performed before radioiodine therapy and showed increased radiotracer uptake at the thyroid remnants and pre-tracheal levels. Additionally, single-photon emission computed tomography combined with CT (SPECT/CT) was performed, and confirmed the areas of intense uptake, in addition to a moderate uptake in the right and left pulmonary parenchyma, suggesting lung metastasis. To conclude, an overall low level of statistical evidence exists regarding poorly differentiated malignancy in substernal goiters, and the data also remains scarce regarding the impact of genetic and molecular configurations, such as the BRAF-positive profile, in this specific instance. Furthermore, multimodal management includes additional diagnosis methods such as SPECT/CT, while long-term multilayered therapy includes tyrosine kinase inhibitors if the outcome shows an iodine-resistant profile with a poor prognosis. Awareness remains a key factor in cases of a poorly differentiated carcinoma presenting as a rapidly growing goiter with substernal extension in an apparently healthy adult. A surgical approach, while varying with the surgeon’s skills, represents a mandatory step to ensure a better prognosis. In addition to a meticulous histological characterization, genetic/molecular features provide valuable information regarding the outcome and can further help with the decision to use new anti-cancer drugs if tumor response upon radioiodine therapy is no longer achieved; such a development is expected in this disease stage in association with a BRAF-positive configuration. Full article

Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone. Full article

Background: Lenvatinib is a receptor tyrosine kinase inhibitor indicated for advanced radioiodine-refractory thyroid cancer (RAI-RTC). It is recommended to start at 24 mg per day; however, in patients who are at risk of severe adverse events, it may be reasonable to start at lower doses. Patients and Methods: We included 15 patients with RAI-RTC who started lenvatinib at a very low/low dose and evaluated the efficacy and safety. Results: Eight patients (53.3%) did not show progression of the disease, and about half of the patients (53.3%) were alive at the last follow-up visit. Up to 26.6% of patients achieved a partial response to therapy, with a notable volume reduction in the local and metastatic lesions. However, 80% of patients experienced adverse events, mainly of a moderate grade. Conclusions: Although these findings are based on a small sample size and a single-center study, treatment with lenvatinib at very low/low doses in fragile patients seems to be a promising strategy for the management of RAI-RTC, balancing effective disease control with a favorable safety profile. Full article

Radioactive iodine therapy has been a well-established treatment for various thyroid conditions since the 1940s, targeting both benign diseases and malignancies. Treatment for benign conditions typically involves low doses of 131I, often requiring no more than two treatments, with the dose either fixed or personalized based on thyroid tissue mass and iodine uptake. In contrast, differentiated thyroid cancer treatment often requires higher doses and multiple administrations, especially for metastatic cases. Recent guidelines and studies have proposed more conservative management strategies, including careful follow-up, due to concerns over the high risk–benefit ratio in selected cases with a low risk of disease recrudescence. Despite its possible efficacy, radioiodine therapy is associated with dose-dependent side effects, the most common of which is salivary gland dysfunction or inflammation, affecting approximately 30% of adult patients. These effects pose significant challenges in nuclear medicine practice. This review aims to summarize the latest evidence on the incidence, impact on quality of life, prevention strategies and the role of these side effects in the decision-making process regarding RAI therapy. Full article

Therapy with radioactive iodine (I-131) following a total thyroidectomy has been a gold standard in the treatment of differentiated thyroid cancer (DTC) for over 80 years. Over the years, its role has shifted from routine use to a more selective, risk-adapted approach, informed by tumor biology, patient risk stratification and evolving clinical guidelines. This review examines the changing landscape of I-131 therapy, tracing its historical foundations, current indications, and future directions shaped by molecular medicine. We discuss the transition from a standardized, one-size-fits-all treatment approach to an individualized, dynamic stratification model that allows for ongoing risk reassessment and tailored treatment strategies. Key updates in clinical practice, such as the 2015 ATA Guidelines, the 2022 ETA Consensus Statement, and joint SNMMI and EANM nuclear medicine recommendations, are critically examined. We also address ongoing controversies in the management of low- and intermediate-risk patients, including the roles of I-131 whole-body scanning, activity selection, and overall treatment approach. Molecular theranostics is ushering in a new era in DTC management, enabling improved patient selection and more precise treatment. Advances in molecular profiling, imaging, and targeted therapies support a personalized treatment approach that aims to optimize therapeutic decisions while minimizing side effects and enhancing long-term safety. Full article

Thyroid cancer (TC) remains a prevalent malignancy, with over 820,000 global cases diagnosed in 2022. Differentiated thyroid carcinoma (DTC), primarily papillary and follicular types, accounts for most cases and has a favorable prognosis with total thyroidectomy and radioiodine (RAI) ablation. However, 5–15% of patients develop RAI-refractory (RAI-R) disease, leading to a significantly poorer outcome. For RAI-R patients, treatment decisions depend on disease progression. Active surveillance is suitable for indolent cases, while symptomatic or progressive disease requires systemic therapy. Multikinase inhibitors (MKIs) such as lenvatinib and sorafenib serve as first-line options, with cabozantinib recently approved for resistant cases. Additionally, novel targeted therapies, including RET and NTRK inhibitors, and immune checkpoint inhibitors, are under investigation, offering a personalized approach. A key challenge is determining the optimal timing for systemic therapy, balancing progression-free survival (PFS) benefits against MKI-related toxicities, which significantly impact quality of life (QoL). Molecular testing can identify actionable mutations, guiding therapy selection. Clinical guidelines (ATA, ESMO) recommend initiating treatment based on disease progression and patient condition, integrating strategies such as active surveillance, surgery, and radiotherapy when appropriate. Despite advances, systemic therapies carry significant adverse events (e.g., hypertension, fatigue, gastrointestinal toxicity), necessitating careful monitoring to prevent dose reductions or interruptions. A multidisciplinary approach is essential to optimize patient outcomes and maintain QoL. As targeted therapies continue to evolve, further research is needed to refine treatment sequencing and improve outcomes for RAI-R TC. This review synthesizes current evidence to guide clinical decision-making. Full article

Background: The understanding of the molecular basis of paediatric thyroid carcinoma has expanded rapidly in the last decade. Most carcinomas are associated with de novo somatic gene alterations that confer distinct clinicopathological characteristics. In comparison to adults, paediatric carcinomas are less commonly associated with point mutations and more commonly with gene fusions, which are characterised by more-invasive disease. Cancer predisposition genes play an important role in a small percentage of tumours, and the family history and the recognition of other syndromic features are key to identifying these patients. Molecular testing platforms for clinical use have been developed and validated in adults, and their use is becoming established in the management of indeterminate thyroid nodules, where they significantly reduce the rates of diagnostic lobectomy. Paediatric data are more limited than adult data, and the role of molecular testing in paediatric thyroid carcinoma management is evolving. Methods: This review describes the current knowledge of molecular alterations in paediatric thyroid carcinomas, evidence supporting molecular testing in clinical practice, and future directions for research. Results and Conclusions: A molecular diagnosis enables the use of molecularly targeted therapies for children and adolescents with advanced or radioiodine-refractory disease. There is also great potential for molecular testing to improve the accuracy of the risk-stratification of paediatric thyroid nodules, reducing surgical intervention and complications without negatively impacting outcomes, and data to support such an approach are emerging. Full article

Background: The exhalation of radioiodine following radioiodine therapy (RIT) presents a challenge in radiation protection, though the mechanisms remain incompletely understood. Previous studies have indicated that radioiodine is predominantly exhaled in an organically bound form in humans. Methods: This study investigates the chemical composition and exhaled amounts of radioiodine, as well as the impact of thyroid-targeted pharmacological interventions, using a controlled mouse model. Female Balb/c mice (25 g) were administered oral doses of radioiodine (0.1, 1, 2, 10, and 23 MBq per animal) with and without prior treatment using thyroid-blocking agents (stable iodine, perchlorate) or antithyroid drugs (carbimazole). Exhaled radioiodine was collected in metabolic cages, separating chemical forms (aerosolized iodine, elemental iodine, organically bound iodine), and quantified via scintillation counter. Results: The exhaled radioiodine activity was proportional to the administered dose (0.2–0.3%). Thyroid-blocking agents increased exhalation, shifting toward elemental iodine. Antithyroid drugs reduced exhalation but increased aerosol formation, particularly at higher I-131 doses. Organically bound iodine remained the predominant exhaled species in all groups. Conclusions: These results highlight the critical role of the thyroid in radioiodine organification. The blockade of thyroid uptake disrupted the formation of organically bound iodine, suggesting that iodine organification requires passage through the thyroid. Additionally, the results support the hypothesis that iodine metabolism outside the thyroid is less efficient, contributing to the formation of organic iodine species. Radical formation is likely a key factor in generating these volatile iodine species, with radiation-induced iodine and methyl radicals playing a role in their formation. Full article

Background: The role of radioiodine (RAI) therapy for differentiated thyroid cancers (DTCs) is still a matter of debate. Low-dose RAI (LDRAI) therapy is a possible treatment for patients at low–intermediate risk of recurrence. The aim of this study was to evaluate the occurrence of post-RAI therapy clinical and biochemical side effects with respect to its dosage. Methods: We retrospectively examined 142 patients who had been administered RAI therapy for DTCs and carried out at least a 12-month follow-up. The incidence of clinical adverse events (CAEs: xerophthalmia, xerostomia, and dysgeusia) and values for hemoglobin (Hb), red blood cells (RBCs), white blood cells (WBCs) and platelets (PLTs) during the first year of follow-up were compared between patients who underwent standard-dose RAI (SDRAI) therapy and LDRAI therapy. Results: Of the 142 patients, 66 were treated with LDRAI and 76 with SDRAI. A higher incidence of CAEs was found in the SDRAI group than in the LDRAI group (p = 0.002). An administered dose above 2849 MBq was associated with CAEs (sensitivity 88.89%, specificity 54.03%, p < 0.001). We found a slight decrease in Hb (p = 0.008), RBCs (p = 0.013), WBCs (p = 0.004) and PLTs (p < 0.001) in the SDRAI group, while in the LDRAI group only WBCs showed a minimal decrease (p = 0.027) with any occurrence of overt bone-marrow disease. Conclusions: According to our data, LDRAI therapy seemed to be associated with a lower incidence of CAEs than SDRAI therapy. Both methods showed an excellent safety profile in terms of hematopoietic effects. However, the effect of SDRAI therapy in this setting might have been more positive than that of LDRAI therapy. Full article

Current therapies for Graves’ disease (GD) primarily aim to manage hyperthyroidism through synthetic antithyroid drugs, radioiodine, or surgery. However, these approaches are often limited by their incomplete efficacy and the risk of inducing hypothyroidism. The latest advances in understanding the autoimmune mechanisms driving GD have paved the way for novel therapies targeting the thyrotropin receptor (TSH-R) or immune pathways. Overall, key targets include cluster of differentiation 20 (CD20), cluster of differentiation 40 (CD40), protein tyrosine phosphatase non-receptor type 22 (PTPN22), cytotoxic T lymphocyte antigen-4 (CTLA-4), B cell-activating factor (BAFF), and the Fc receptor-like protein 3 (FcRL3). Recent preclinical studies and clinical trials testing targeted therapies have shown promising results in terms of efficacy and safety. Here, we present a narrative review of the literature on emerging therapeutic approaches for GD that are currently under investigation. Full article

Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or neonatal hyperthyroidism. This immunological effect should be weighed against the risk of congenital malformation taking propylthiouracil during pregnancy. For up to 2 years after radioiodine therapy for Graves’ disease, TRAb levels may remain above the pre-therapeutic level. The time of conception after radioiodine therapy and a high TRAb level are associated with the likelihood of neonatal hyperthyroidism: 8.8% probability if conception occurred 6–12 months after radioiodine therapy, with a 5.5% probability for 12–18 months, and 3.6% probability for 18–24 months. The TRAb value above 10 U/L in the third trimester is the main risk factor for neonatal hyperthyroidism. If a woman does not wish to postpone her family planning, the pre-conceptional counseling has to describe the risk of propylthiouracil, thiamazole, or of an uncontrolled hyperthyroidism. According to some national cohort studies (Danish, Swedish, Korean), the risk for fetal malformations (ear, urinary tract) under propylthiouracil is increased by 1.1–1.6%, in addition to the spontaneous risk for unexposed pregnant women. For thiamazole, the additional risk for fetal malformation was about 2–3%, depending on the dose of thiamazole. Propylthiouracil has posed a lower risk for congenital malformation than an uncontrolled hyperthyroidism. To minimize the risk for the newborn, women with Graves’ disease and hyperthyroidism should offer a definitive therapy strategy (e.g., radioiodine therapy) long before planning a pregnancy. Full article

Background: Advancements in therapeutic approaches and standard medical interventions have significantly improved the prognosis of patients with differentiated thyroid cancer. However, uncertainties remain regarding the optimal timing and protocols for dental implant placement in patients undergoing radioiodine-131 (I-131) therapy. Debates continue about the potential effects of radiation on osseointegration dynamics and implant viability. This in vitro study assessed the impact of radiodiodine-131 (I-131) used for differentiated thyroid cancer on the structure of zirconia and titanium implants. Methods: A total of 60 implants were utilized, with distribution into two cohorts: titanium implants (Ti, n = 30) and zirconia implants (Zr, n = 30). Subsequently, the Ti and Zr implants were immersed in I-131 solution and retrieved at specified time intervals: 0, 6, 12, 24, 48 h, and 8 days post irradiation. The analyses used to characterize the structure of the implants were radioactivity, scanning electron microscopy, atomic force microscopy, roughness, and Vickers hardness assessment. Results: The findings indicate that the zirconia implants exhibited minimal ultra-structural topographic changes after irradiation. Notable topographical changes and debris deposition on zirconia surfaces became evident after 24 h, with cumulative effects observed after 192 h. The titanium implants, on the other hand, showed surface alterations beginning at 12 h of exposure. Significant changes, including erosive patterns and substantial debris deposits, occurred after 48 and 192 h, leading to increased surface roughness by 24 h. Implants exposed for 12 and 24 h formed a statistically significant group, indicating the onset of surface alteration accumulation. The erosion debris confirmed the surface alterations induced by radioiodine-131 exposure. Conclusions: Overall, the Zr implants demonstrated greater stability compared to the Ti implants following radioiodine-131 exposure. Full article

Purpose: Radiotherapy treatments are known to alter the gut microbiota. However, little is known regarding the effect of nuclear medicine treatments on gut microbiota, and it is established that nuclear medicine is inherently different from radiotherapy. To address this knowledge gap, we conducted a prospective study to identify changes in the gut microbiota of patients treated with [¹³¹I]NaI by comparing fecal samples before and after RAIT. Methods: Fecal samples of 64 patients (37 with thyroid cancer and 27 with hyperthyroidism) with indication for RAIT were collected 2 to 3 days before treatment and 8 to 10 days post-treatment. After DNA extraction, the gut microbiota’s richness, diversity, and composition were analyzed by shotgun metagenomics. In addition, LEfSe was performed to compare compositional changes in specific bacteria. Results: Gut microbiome richness and diversity remained unchanged after RAIT, with few changes in its composition identified, especially in patients with hyperthyroidism. Conclusions: This study provides a conceptual and analytical basis for increasing our understanding of the effects of radiopharmaceuticals on gut microbiota. Our preliminary results indicate that RAIT, contrary to radiotherapy, does not cause major disruptions to the human gut microbiota. Full article

Bisphenol A (BPA) is a prevalent environmental contaminant found in plastics and known for its endocrine-disrupting properties, posing risks to both human health and the environment. Despite its widespread presence, the impact of BPA on papillary thyroid cancer (PTC) progression, especially under realistic environmental conditions, is not well understood. This study examined the effects of BPA on PTC using a 3D thyroid papillary tumor spheroid model, which better mimicked the complex interactions within human tissues compared to traditional 2D models. Our findings demonstrated that BPA, at environmentally relevant concentrations, could induce significant changes in PTC cells, including a decrease in E-cadherin expression, an increase in vimentin expression, and reduced thyroglobulin (TG) secretion. These changes suggest that BPA exposure may promote epithelial–mesenchymal transition (EMT), enhance invasiveness, and reduce cell differentiation, potentially complicating treatment, including by increasing resistance to radioiodine therapy. This research highlights BPA’s hazardous nature as an environmental contaminant and emphasizes the need for advanced in vitro models, like 3D tumor spheroids, to better assess the risks posed by such chemicals. It provides valuable insights into the environmental implications of BPA and its role in thyroid cancer progression, enhancing our understanding of endocrine-disrupting chemicals. Full article

Background: Struma ovarii (SO) is an ovarian teratoma with the presence of ectopic thyroid tissue. Differentiated thyroid cancer (DTC) in SO is a rare finding. Management of DTC in SO is currently not clearly established. We performed a systematic review of the literature to assess the role of 131I radiometabolic therapy in the treatment of DTC in SO. Methods: a wide literature search in the Scopus, PubMed/MEDLINE, and Web of Science databases was made to find published articles regarding the treatment of patients with DTC and SO. The quality assessment of studies was performed by QUADAS-2 evaluation. Results: eleven studies were included in the systematic review. All of them were retrospective studies and/or case series, and two of them also included a review of the literature. Most of the studies describe cases of DTC in SO treated by total thyroidectomy (TT) and subsequent radioiodine (RAI) therapy, especially in patients with distant metastases and/or concomitant thyroid cancer. However, the majority of patients apparently did not require radiometabolic therapy. Conclusions: TT and subsequent RAI therapy is usually performed in metastatic disease, not recommended in patients with intraovarian disease without risk factors, and it appeared possible but not mandatory in patients with risk factors. Full article